A highly attenuated vaccinia virus strain LC16m8-based vaccine for severe fever with thrombocytopenia syndrome

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) caused by a species Dabie bandavirus (formerly SFTS virus [SFTSV]) is an emerging hemorrhagic infectious disease with a high case-fatality rate. One of the best strategies for preventing SFTS is to develop a vaccine, which is expected to induce both humoral and cellular immunity. We applied a highly attenuated but still immunogenic vaccinia virus strain LC16m8 (m8) as a recombinant vaccine for SFTS. Recombinant m8s expressing SFTSV nucleoprotein (m8-N), envelope glycoprotein precursor (m8-GPC), and both N and GPC (m8-N+GPC) in the infected cells were generated. Both m8-GPC- and m8-N+GPC-infected cells were confirmed to produce SFTSV-like-particles (VLP) in vitro, and the N was incorporated in the VLP produced by the infection of cells with m8-N+GPC. Specific antibodies to SFTSV were induced in mice inoculated with each of the recombinant m8s, and the mice were fully protected from lethal challenge with SFTSV at both 103 TCID50 and 105 TCID50. In mice that had been immunized with vaccinia virus strain Lister in advance of m8-based SFTSV vaccine inoculation, protective immunity against the SFTSV challenge was also conferred. The pathological analysis revealed that mice immunized with m8-GPC or m8-N+GPC did not show any histopathological changes without any viral antigen-positive cells, whereas the control mice showed focal necrosis with inflammatory infiltration with SFTSV antigen-positive cells in tissues after SFTSV challenge. The passive serum transfer experiments revealed that sera collected from mice inoculated with m8-GPC or m8-N+GPC but not with m8-N conferred protective immunity against lethal SFTSV challenge in naïve mice. On the other hand, the depletion of CD8-positive cells in vivo did not abrogate the protective immunity conferred by m8-based SFTSV vaccines. Based on these results, the recombinant m8-GPC and m8-N+GPC were considered promising vaccine candidates for SFTS.

Safety, Immunogenicity and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Bandaviruses

“…This has caused the WHO to list SFTSV in its prioritized pathogen research blueprint and the NIAID to include it as a category C priority pathogen (26,27). In response to the potential threat from SFTSV, many SFTSV vaccines are being developed using a variety of different technologies including protein subunit, DNA, and recombinant viral platforms (35,36,38,39,62,63).…”

“…Ifnar -/mice are susceptible to lethal SFTSV challenge and have therefore been used to evaluate an array of SFTSV vaccines that use DNA, protein subunit, and recombinant viral technologies (36,38,39,62). A DNA vaccine encoding the ectodomains of Gn and Gc and a chimeric N-NSs fusion protein on a single plasmid only protected 40% of mice from lethal challenge after three doses of vaccine (62).…”

“…Despite these difficulties, several groups have designed and tested SFTSV vaccines, primarily using Ifnar -/mice. Tested vaccine platforms include DNA, virus-vectored, and attenuated recombinant SFTSV vaccines (35)(36)(37)(38)(39).…”

Vaccine Development for Severe Fever with Thrombocytopenia Syndrome

“…A study reported the possibility of recombinant m8 strains that possess the coding regions of SFTSV N (m8-N), GPC (m8-GPC), or both N and GPC (m8-N+GPC) (m8-based SFTSV vaccines) as SFTS vaccine candidates [64]. These m8-based SFTSV vaccines express SFTSV genes in the infected cells, and especially the cells infected with m8-GPC or m8-N+GPC produce SFTS VLP in culture supernatant in vitro.…”

Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2

“…Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel tick-borne virus ( Dabie bandavirus , formerly SFTS virus and Huaiyangshan banyangvirus ), which belongs to the genus Bandavirus , family Phenuiviridae , order Bunyavirales ( Yoshikawa et al, 2021 ). Genome of the virus consists of three negative-stranded RNA segments, encoding four proteins, including RNA-dependent RNA polymerase (RdRp), glycoprotein precursor (GPC), nucleoprotein (N), and nonstructural protein (NSs).…”